Volume 52 Issue 10, October 2020

The WashU Virus Genome Browser is a web-based portal for efficient visualization of viral ‘omics’ data in the context of a variety of annotation tracks and host infection responses. The browser features both a phylogenetic-tree-based view and a genomic-coordinate, track-based view in which users can analyze the sequence features of viral genomes, sequence diversity among viral strains, genomic sites of diagnostic tests, predicted immunogenic epitopes and a continuously updated repository of publicly available genomic datasets.

The UCSC SARS-CoV-2 Genome Browser (https://genome.ucsc.edu/covid19.html) is an adaptation of our popular genome-browser visualization tool for this virus, containing many annotation tracks and new features, including conservation with similar viruses, immune epitopes, RT–PCR and sequencing primers and CRISPR guides. We invite all investigators to contribute to this resource to accelerate research and development activities globally.

The emergence of the COVID-19 pandemic has spurred a global rush to uncover basic biological mechanisms to inform effective vaccine and drug development. Despite the novelty of the virus, global sequencing efforts have already identified genomic variation across isolates. To enable easy exploration and spatial visualization of the potential implications of SARS-CoV-2 mutations in infection, host immunity and drug development, we have developed COVID-3D (http://biosig.unimelb.edu.au/covid3d/).

FOXA1 is a key pioneer factor in androgen-receptor activity but has been an elusive drug target. A new study shows that inhibition of the associated cofactor LSD1 modifies the methylation state of FOXA1, thus resulting in chromatin dissociation and tumor inhibition, even in models of treatment-resistant prostate cancer.

How do boundary elements divide chromosomes into domains? A new study uses random genomic insertions to show how small genomic fragments can shape chromatin folding through the interplay of loop extrusion and compartmentalization. Spoiler: context matters.

This Perspective discusses important aspects of data generation, infrastructure and management that affect how the research community uses medical data, including genetic and genomic information.

LSD1 promotes FOXA1 chromatin binding by demethylating lysine 270 of FOXA1 in prostate cancer cells. LSD1 inhibition decreases growth of prostate cancer cells.

Haplotype-resolved assembly of a heterozygous diploid potato, RH89-039-16, and identification of deleterious mutations provide insights into the genome organization and breeding of a clonally propagated diploid species.

Multi-omic profiling of brain tissue from patients with Alzheimer’s disease (AD) identifies gains in H3K27ac and H3K9ac linked to transcription and disease pathways. Increasing H3K27ac and H3K9ac in a fly model of AD exacerbates neurodegeneration.

An analysis of 3,757 Sardinian genomes identifies 122 association signals for 459 immune cell traits at 69 loci. Some variants are associated with autoimmune disorders.

Whole-exome sequencing of 250 parent–offspring trios identifies an enrichment of rare damaging de novo mutations in individuals with cerebral palsy and implicates genetically mediated dysregulation of early neuronal connectivity in the etiology of this disorder.

Mathematical modeling of evolutionary dynamics of neoantigens and immune escape in growing tumors shows that strong negative selection for neoantigens inhibits tumor growth but also provides a strong selective pressure for the evolution of immune escape.

A massively parallel reporter assay (eSTARR-seq) shows that gene-distal transcription start sites can delineate active enhancers with higher resolution than histone modifications.

Insertion of a tissue-invariant chromatin domain boundary into 16 ectopic loci leads to various structural phenotypes, which depend on local chromatin features, CTCF binding and transcriptional status.

NSD1, which deposits H3K36me2, is a major regulator of DNA methylation in male but not in female gametogenesis. NSD1 safeguards against H3K27me3-associated transcriptional silencing.

Whole-genome sequence analysis of 172 indigenous African cattle from 16 breeds identifies 16 loci linked to environmental adaptations among crossbred animals, including a highly divergent locus in African taurine cattle putatively linked to trypanotolerance.

A study of 580 tomato lines resulting from a cross between a wild desert-adapted species and a domesticated cultivar elucidates the genetic basis of gene expression and metabolite variation associated with fruit traits and defense against pathogens.

Mendelian randomization (MR) and colocalization analyses are used to estimate causal effects of 1,002 plasma proteins on 225 phenotypes. Evidence from drug developmental programs shows that target-indication pairs with MR and colocalization support were more likely to be approved, highlighting the value of this approach for prioritizing therapeutic targets.